The Breast Oncology Program (BOP), co-directed by Daniel F. Hayes, M.D. and Sofia D. Merajver, M.D., conducts basic, translational, and clinical research covering the spectrum of breast cancer. The BOP has six major scientific themes: 1) elucidation of the molecular mechanism of regulation of normal and malignant breast tissues and cells; 2) development of tools for diagnosis, prognosis, and monitoring; 3) development of novel therapeutic strategies; 4) evaluation of risk assessment and prevention strategies; 5) Improvement in quality of life and survivorship issues for patients with breast cancer; and 6) health services research. The BOP has 49 members from 11 Departments within.5 Schools of the University of Michigan, ensuring broad multi-disciplinary collaborations. Indeed, of the 397 publications by program members over this grant period, 20% were Intra-programmatic and 44% were inter-programmatic collaborations. Members of the UM BOP receive over $14,2 million In annual direct peer-reviewed funding of which $4 million Is from the NCI. During this period, BOP investigators have 1) characterized the breast cancer stem cell and conducted a phase 1 trial of chemotherapy plus a gamma secretase Inhibitor, 2) performed pre-clinical studies and Introduced a novel agent that inhibits the inhibitor of apoptosis proteins (lAPs) into clinical trial; 3) studied RhoC proteins, cancer cell matrix transport, epithelial-mesenchymal transition, and chemokine mediation of metastasis; 4) performed pre- and clinical studies of circulating tumor cells; 5) advanced understanding of transcriptional regulation, DNA repair, and cancer genetics, of breast epithelial tumorigenesis; 6) Identified translocations involving the MAST and NOTCH genes 7) demonstrated intrinsic subtypes that are resistant to adjuvant chemotherapy; 8) Investigated pharmacogenetics of breast cancer treatment; and 9) furthered the breast cancer survivorship and quality of life. The BOP has a major commitment to health services and outcomes research, with Important observations regarding patient decision. The BOP will continue these important pre-clinical, translational, and clinical studies in the upcoming funding period, particularly focusing on discovery of new diagnostic and therapeutic targets.